Metabolic Versatility in Melainabacteria, a Close Relative of Cyanobacteria

A New Member of Melainabacteria, the Closest Relatives of Cyanobacteria Melainabacteria are the recently discovered, closest non-photosynthetic relatives of cyanobacteria, the organisms responsible for the oxygenation of Earth\u27s atmosphere. Previous work has shown that Melainabacteria live in a wide range of environments, including deep groundwater, anoxic sediments, and the digestive tracts of termites and mammals. These bacteria have been suggested to play a significant role in the latter environments and may contribute to neurodegenerative and gastrointestinal disease in human populations. However, our knowledge of Melainabacteria diversity and metabolism is still very limited, principally because no member of this group has been successfully cultured in the laboratory. Recently, DNA sequencing has revealed that a member of the Melainabacteria is growing in co-culture with an established diatom strain at the University of Montana’s Miller lab. In this study, we obtained a nearly complete Melainabacteria genome from metagenomic sequencing data. We then compared this genome to other previously sequenced Melainabacteria genomes to better understand genome architecture and the metabolic capacity of this bacterium. These data will guide further culturing efforts and future experiments. Together, our work will help clarify the functional role(s) of Melainabacteria in its environment and how it “makes a living” energetically. It will also provide new insights regarding the metabolic capabilities of the cyanobacterial ancestor and the origin of oxygenic photosynthesis

A note on isoparametric polynomials

We show that any homogeneous polynomial solution of |\nabla F(x)|^2=m^2|x|^(2m-2), m>1, is either a radially symmetric polynomial F(x)=\pm |x|^m (for even m's) or it is a composition of a Chebychev polynomial and a Cartan-M\"unzner polynomial.Comment: 6 page

Representations and classification of traveling wave solutions to Sinh-G{\"o}rdon equation

Two concepts named atom solution and combinatory solution are defined. The classification of all single traveling wave atom solutions to Sinh-G{\"o}rdon equation is obtained, and qualitative properties of solutions are discussed. In particular, we point out that some qualitative properties derived intuitively from dynamic system method aren't true. In final, we prove that our solutions to Sinh-G{\"o}rdon equation include all solutions obtained in the paper[Fu Z T et al, Commu. in Theor. Phys.(Beijing) 2006 45 55]. Through an example, we show how to give some new identities on Jacobian elliptic functions.Comment: 12 pages. accepted by Communications in theoretical physics (Beijing

Engineering the Redox Potential over a Wide Range within a New Class of FeS Proteins

Abstract: MitoNEET is a newly discovered mitochondrial protein and a target of the TZD class of antidiabetes drugs. MitoNEET is homodimeric with each protomer binding a [2Fe-2S] center through a rare 3-Cys and 1-His coordination geometry. Both the fold and the coordination of the [2Fe-2S] centers suggest that it could have novel properties compared to other known [2Fe-2S] proteins. We tested the robustness of mitoNEET to mutation and the range over which the redox potential (EM) could be tuned. We found that the protein could tolerate an array of mutations that modified the EM of the [2Fe-2S] center over a range of ∼700 mV, which is the largest EM range engineered in an FeS protein and, importantly, spans the cellular redox range (+200 to-300 mV). These properties make mitoNEET potentially useful for both physiological studies and industrial applications as a stable, water-soluble, redox agent

Ataluren treatment of patients with nonsense mutation dystrophinopathy

Introduction: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. Methods: Randomized, double‐blind, placebo‐controlled study; males ≥5 years with nm‐dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N = 57); ataluren 20, 20, 40 mg/kg (N = 60); or placebo (N = 57) for 48 weeks. The primary endpoint was change in 6‐Minute Walk Distance (6MWD) at Week 48. Results: Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Δ = 31.3 meters, post hoc P = 0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg, and placebo. Conclusions: As the first investigational new drug targeting the underlying cause of nm‐dystrophinopathy, ataluren offers promise as a treatment for this orphan genetic disorder with high unmet medical need

Suitability of external controls for drug evaluation in Duchenne muscular dystrophy

OBJECTIVE: To evaluate the suitability of real-world data (RWD) and natural history data (NHD) for use as external controls in drug evaluations for ambulatory Duchenne muscular dystrophy (DMD). METHODS: The consistency of changes in the 6-minute walk distance (Δ6MWD) was assessed across multiple clinical trial placebo arms and sources of NHD/RWD. Six placebo arms reporting 48-week Δ6MWD were identified via literature review and represented 4 sets of inclusion/exclusion criteria (n = 383 patients in total). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total). Mean Δ6MWD was compared between each placebo arm and RWD/NHD source after subjecting the latter to the inclusion/exclusion criteria of the trial for baseline age, ambulatory function, and steroid use. Baseline covariate adjustment was investigated in a subset of patients with available data. RESULTS: Analyses included ∼1,200 patient-years of follow-up. Differences in mean Δ6MWD between trial placebo arms and RWD/NHD cohorts ranged from -19.4 m (i.e., better outcomes in RWD/NHD) to 19.5 m (i.e., worse outcomes in RWD/NHD) and were not statistically significant before or after covariate adjustment. CONCLUSIONS: We found that Δ6MWD was consistent between placebo arms and RWD/NHD subjected to equivalent inclusion/exclusion criteria. No evidence for systematic bias was detected. These findings are encouraging for the use of RWD/NHD to augment, or possibly replace, placebo controls in DMD trials. Multi-institution collaboration through the Collaborative Trajectory Analysis Project rendered this study feasible

Rapid Evolution of the Rhopalodia gibba Mitochondrion in the Presence of an Emerging Nitrogen Fixing Organelle

The evolution of the mitochondrion from an endosymbiotic bacterium was the defining moment in the origin of eukaryotes. This understanding is based on multiple evolutionary studies that show that some organelles, such as mitochondria and chloroplasts, evolved from endosymbionts. Yet, understanding the process of organelle evolution remains one of the grand challenges in biology. Although several host-microbe relationships have been studied as key steps in organelle evolution, these examples typically focus on later stages of this process. The diatoms in the genera Rhopalodia, Epithemia, and Denticula have nitrogen fixing cyanobacterial endosymbionts called spheroid bodies, which are proposed to be emerging organelles. Understanding this diatom-spheroid body relationship provides an important model of that can provide insight into the early stages of how organelles evolve. To understand this system, we obtained genome data for the spheroid body as well as the first genome data for the host, Rhopalodia gibba. We are using these data to investigate evolutionary changes in spheroid body and host genomes during the development of the symbiosis as well as to serve as references for mapping gene expression data. In this study, we compared the genome of the R. gibba organelles to other closely related diatom species that don’t have spheroid bodies. Analyses show that the chloroplast genome is changing at a similar rate compared to related diatoms. However, selection on the R. gibba mitochondrion appears to be relaxed. Translational genes appear to be changing at an increased rate compared to energy production genes. Additionally, horizontal gene transfer also contributes to mitochondrial divergence. This diatom-spheroid body relationship provides a rare opportunity to quantify these benefits and costs and could help elucidate the mechanisms of organelle evolution